23898
Maternal Whole Blood Serotonin Levels Are Inversely Correlated with Social Difficulty, Language Impairment, and Repetitive Behavior in Offspring with Autism Spectrum Disorder.
Biomarker, neuroimaging and genetic findings implicate the serotonin (5-HT) system in autism spectrum disorder (ASD). Several groups have investigated clinical correlates of 5-HT levels in ASD, with minimal and inconsistent findings across studies. Recently, we identified an impact of the maternal 5-HT system on embryonic forebrain 5-HT levels and neurodevelopment in mice (Muller et al., in press).
Objectives:
As an initial step in evaluating the contribution of the maternal 5-HT system to ASD risk, we hypothesized that mothers’ serotonin levels would correlate with the clinical presentation of ASD in their offspring.
Methods:
Whole blood serotonin (WB5-HT) levels were obtained from 184 children diagnosed with Autistic Disorder, Asperger’s Disorder, or Pervasive Developmental Disorder Not Otherwise Specified based on DSM-IV-TR criteria, as well as from 90 of their fathers and 105 of their mothers. The child social and repetitive behavior phenotypes were evaluated using the Autism Diagnostic Observation Schedule (ADOS-2, Lord et al., 2012). Language function was examined using the Peabody Picture Vocabulary Test (PPVT-4, Dunn & Dunn, 2006) and the Expressive One-Word Picture Vocabulary Test (EOWPVT-4, Martin & Brownell, 2000). Finally, adaptive function was assessed using the Vineland Adaptive Behavior Scale (VABS-2, Sparrow, Cicchetti & Balla, 2005). Participants or parents receiving medications influencing the 5-HT system, such as serotonin reuptake inhibitors, were excluded from analysis. Whole blood samples obtained by venipuncture were stored in Vacutainer tubes containing EDTA at -70° C, prior to WB5-HT assay by high-performance liquid chromatography.
Results:
Proband WB5-HT levels correlated with both maternal WB5-HT levels (rs(99)=0.291, p=0.003) and paternal WB5-HT levels (rs(88)=0.385, p=0.0002). Despite these within family correlations, maternal WB5-HT levels were significantly correlated with child social, language, and repetitive behavior phenotypes; whereas paternal WB5-HT levels and proband levels were not. Maternal WB5-HT levels were negatively correlated with ADOS-2 total scores of social affect (rs(103)=-0.258, p=0.008), total scores of restricted and repetitive behavior (rs(103)=-0.254, p=0.009) and overall ADOS-2 scores of social affect and restricted, repetitive behavior (rs(103)=-0.300, p=0.002). Maternal WB5-HT levels correlated with language raw scores on the PPVT-4 and EOWPVT-4 (rs(71)=0.386, p=0.001 and rs(62)=0.421, p=0.001, respectively). Finally, maternal WB5-HT levels correlated with overall adaptive functioning on the VABS-2 (composite standard score, rs(99)=0.268, p=0.007), and with standard scores in the communication and living skills domains (rs(99)=0.291, p=0.003 and rs(99)=0.328, p=0.001, respectively).
Conclusions:
We found that higher levels of maternal WB5-HT levels were associated with lower impairment in social and repetitive behavior, as well as higher language scores, reflecting less communication impairment in children with ASD. Work is ongoing to replicate these findings and assess whether maternal 5-HT levels define a specific subgroup of children with ASD. Future studies using animal models and longitudinal neuroimaging are needed to understand the mechanisms underlying these associations.